Pdif-mediated antibiotic resistance genes transfer in bacteria identified by pdifFinder. Issue 1 (5th December 2022)

• Record Type: Journal Article
• Authors: Shao, Mengjie; Ying, Nanjiao; Liang, Qian; Ma, Nan; Leptihn, Sebastian; Yu, Yunsong; Chen, Huan; Liu, Chengzhi; Hua, Xiaoting
• Is Part Of: Briefings in bioinformatics. Volume 24:Issue 1(2023)
• Publication Date: 2022-12-05
• Subjects: mobile genetic elements -- XerCD-dif site-specific recombination system -- pdif-ARGs module -- resistance -- ARGs transfer -- plasmids; Genetics -- Data processing -- Periodicals; Molecular biology -- Data processing -- Periodicals; Genomes -- Data processing -- Periodicals; 572.80285
• DOI: 10.1093/bib/bbac521
• Languages: English
• ISSNs: 1467-5463

Abstract

Abstract: Modules consisting of antibiotic resistance genes (ARGs) flanked by inverted repeat Xer-specific recombination sites were thought to be mobile genetic elements that promote horizontal transmission. Less frequently, the presence of mobile modules in plasmids, which facilitate a p dif -mediated ARGs transfer, has been reported. Here, numerous ARGs and toxin-antitoxin genes have been found in p dif site pairs. However, the mechanisms underlying this apparent genetic mobility is currently not understood, and the studies relating to p dif -mediated ARGs transfer onto most bacterial genera are lacking. We developed the web server pdifFinder based on an algorithm called PdifSM that allows the prediction of diverse p dif -ARGs modules in bacterial genomes. Using test set consisting of almost 32 thousand plasmids from 717 species, PdifSM identified 481 plasmids from various bacteria containing p dif sites with ARGs. We found 28-bp-long elements from different genera with clear base preferences. The data we obtained indicate that XerCD- dif site-specific recombination mechanism may have evolutionary adapted to facilitate the p dif -mediated ARGs transfer. Through multiple sequence alignment and evolutionary analyses of duplicated p dif -ARGs modules, we discovered that p dif sites allow an interspecies transfer of ARGs but also across different genera. Mutations in p dif sites generate diverse arrays of modules which mediate multidrug-resistance, as these contain variable numbers of diverse ARGs, insertion sequences and other functional genes. The identification of p dif -ARGs modules and studies focused on the mechanism of ARGs co-transfer will help us to understand and possibly allow controlling the spread of MDR bacteria in clinical settings. The pdifFinder code, standalone software package and description with tutorials are available at https://github.com/mjshao06/pdifFinder .